Synthesis of Chiral TFA-Protected α-Amino Aryl-Ketone Derivatives with Friedel–Crafts Acylation of α-Amino Acid N-Hydroxysuccinimide Ester

Chiral N-protected alpha-amino aryl-ketones are one of the useful precursors used in the synthesis of various biologically active compounds and can be constructed via Friedel-Crafts acylation of N-protected alpha-amino acids. One of the drawbacks of this reaction is the utilization of toxic, corrosive and moisture-sensitive acylating reagents. In peptide construction via amide bond formation, N-hydroxysuccinimide ester (OSu), which has high storage stability, can react rapidly with amino components and produces fewer side reactions, including racemization. This study reports the first synthesis and utilization of N-trifluoroacetyl (TFA)-protected alpha-amino acid-OSu as a potential acyl donor for Friedel-Crafts acylation into various arenes. The TFA-protected isoleucine derivative and its diastereomer TFA-protected allo-isoleucine derivative were investigated to check the retention of alpha-proton chirality in the Friedel-Crafts reaction. Further utilization of OSu in other branched-chain and unbranched-chain amino acids results in an adequate yield of TFA-protected alpha-amino aryl-ketone without loss of optical purity

Combined small cell lung carcinoma and giant cell carcinoma: a case report

Abstract Background Combined small cell lung carcinoma (SCLC) is defined as SCLC combined with elements of non-small cell lung carcinoma (NSCLC), accounting for approximately 30% of cases of SCLC. However, combined SCLC and giant cell carcinoma (GC) is very rare. Case presentation A 50-year-old woman with a 45 pack-year smoking history was referred to our hospital for further investigation of an abnormal left hilar shadow. Chest computed tomography (CT) revealed a 28-mm solid pulmonary nodule in the left lower lobe and an enlarged left hilar lymph node adjacent to the left main pulmonary artery. CT-guided biopsy of the pulmonary nodule led to the diagnosis of high-grade neuroendocrine carcinoma. The preoperative clinical stage was defined as cT1bN1M0. Thus, the patient underwent left lower lobectomy with ND2a-2 lymph node dissection via thoracotomy. Pathological investigation revealed a 22-mm tumor and dense sheet-like growth of small tumor cells with scant cytoplasm and finely granular nuclear chromatin. Moreover, there was a sheet-like growth of bizarre, highly pleomorphic mono- or occasionally multinucleated giant cells, accounting for approximately 40% of the tumor. Both the small and giant cell components were thyroid transcription factor-1-positive and p40-negative and exhibited neuroendocrine differentiation, as indicated by positivity for synaptophysin and CD56 and negativity for chromogranin A. While the small cell component was E-cadherin-positive and vimentin-negative, the giant cell component was E-cadherin-negative and vimentin-positive, indicating an epithelial-to-mesenchymal transition. Only the small cell component was found within the mediastinal and hilar lymph nodes. The final pathological diagnosis was combined SCLC and GC, pT1bN2M0, and pStage IIIA. The patient received adjuvant chemotherapy with 4 cycles of cisplatin and irinotecan. No sign of recurrence has been noted for 1 year after the surgery. Conclusions This is the first detailed report of a unique case with combined SCLC and GC. The coexistence of SCLC and GC in the presented case might indicate several possibilities: (1) GC may arise from SCLC via epithelial-to-mesenchymal transition, (2) SCLC may arise from GC through phenotypic conversion, and (3) SCLC and GC may have derived from a common neuroendocrine origin. Further investigation is necessary to reveal the underlying pathological process

First Detection of Hydroxyl Radical Emission from an Exoplanet Atmosphere: High-dispersion Characterization of WASP-33b Using Subaru/IRD

We report the first detection of a hydroxyl radical (OH) emission signature in the planetary atmosphere outside the solar system, in this case, in the day-side of WASP-33b. We analyze high-resolution near-infrared emission spectra of WASP-33b taken using the InfraRed Doppler spectrograph on the 8.2-m Subaru telescope. The telluric and stellar lines are removed using a de-trending algorithm, SysRem. The residuals are then cross-correlated with OH and H$_{2}$O planetary spectrum templates produced using several different line-lists. We check and confirm the accuracy of OH line-lists by cross-correlating with the spectrum of GJ 436. As a result, we detect the emission signature of OH at $K_\mathrm{p}$ of 230.9$^{+6.9}_{-7.4}$ km s$^{-1}$ and $v_{\mathrm{sys}}$ of $-$0.3$^{+5.3}_{-5.6}$ km s$^{-1}$ with S/N of 5.4 and significance of 5.5$\sigma$. Additionally, we marginally detect H$_{2}$O emission in the H-band with S/N of 4.0 and significance of 5.2$\sigma$ using the POKAZATEL line-list. However, no significant signal is detected using the HITEMP 2010, which might be due to differences in line positions and strengths, as well as the incompleteness of the line-lists. Nonetheless, this marginal detection is consistent with the prediction that H$_{2}$O is mostly thermally dissociated in the upper atmosphere of the ultra-hot Jupiters. Therefore, along with CO, OH is expected to be one of the most abundant O-bearing molecules in the day-side atmosphere of ultra-hot Jupiters and should be considered when studying their atmosphere.Comment: Accepted for publication on ApJL; 12 pages, 6 figure

A spectroscopic thermometer: individual vibrational band spectroscopy with the example of OH in the atmosphere of WASP-33b

Individual vibrational band spectroscopy presents an opportunity to examine exoplanet atmospheres in detail by distinguishing where the vibrational state populations of molecules differ from the current assumption of a Boltzmann distribution. Here, retrieving vibrational bands of OH in exoplanet atmospheres is explored using the hot Jupiter WASP-33b as an example. We simulate low-resolution spectroscopic data for observations with the JWST's NIRSpec instrument and use high resolution observational data obtained from the Subaru InfraRed Doppler instrument (IRD). Vibrational band-specific OH cross section sets are constructed and used in retrievals on the (simulated) low and (real) high resolution data. Low resolution observations are simulated for two WASP-33b emission scenarios: under the assumption of local thermal equilibrium (LTE) and a toy non-LTE model for vibrational excitation of selected bands. We show that mixing ratios for individual bands can be retrieved with sufficient precision to allow the vibrational population distributions of the forward models to be reconstructed. A simple fit for the Boltzmann distribution in the LTE case shows that the vibrational temperature is recoverable in this manner. For high resolution, cross-correlation applications, we apply the individual vibrational band analysis to an IRD spectrum of WASP-33b, applying an 'un-peeling' technique. Individual detection significances for the two strongest bands are shown to be in line with Boltzmann distributed vibrational state populations consistent with the effective temperature of the WASP-33b atmosphere reported previously. We show the viability of this approach for analysing the individual vibrational state populations behind observed and simulated spectra including reconstructing state population distributions.Comment: Submitted for publication in A